The Side Effects and Adverse Clinical Cases Reported after COVID-19 Immunization

COVID-19 remains a deadly disease that poses a serious threat to humanity. COVID-19 vaccines protect the public and limit viral spread. However, public acceptance is significantly dependent on the efficacy and side effects (SEs) of the vaccinations being produced. Four important mechanisms have been examined for COVID-19 vaccines: DNA-based, mRNA-based, protein-based, and inactivated viruses. Vaccination safety research was formerly limited to manufacturer-sponsored studies, but numerous additional cross-sectional survey-based studies conducted globally have contributed to the generation of vaccine-related safety data reports. Twenty-seven studies and twenty-four case reports published-up till 2021 were overviewed for the presentation of SEs and their severity. Injection site pain remained the most dominant localized SE, while headache and fatigue were the most prevalent systemic SEs. Most studies reported that all vaccinations were safe, with very little or no adverse effects, but the nature of SEs was reported to be more persistent in DNA- and mRNA-based vaccines, while inactivated viral vaccines were associated with longer-duration SEs. Overall, SEs were found to be more dominant in women and youngsters. Case reports of adverse reactions have also been documented, but there is still a need to find out their pathological linkage with the COVID-19 vaccination.


Need for Vaccination against COVID-19
Vaccines can be used to control infectious diseases, and are well known to be effective in fostering a long-lasting immune memory. Vaccines currently save the lives of 2-3 million people each year. When recommending or rejecting vaccinations, the adverse effects on people's trust in healthcare professionals should be considered [1]. Severe acute respiratory syndrome-coronavirus-2 (SARS-CoV-2) triggered a pandemic. The first cases were reported in Asia, which were then spread to other parts of the globe [2]. The COVID-19 infection is caused by SARS-CoV-2, against which immunity can be obtained either by natural or preventative immunization of the population at the mass level [3]. The COVID-19 pandemic has introduced a challenge never before seen in the history of humankind for a secure and fearless existence [4], as it has directly afflicted millions of people around the globe. International agencies have recently discovered that poverty and hunger may kill far more people than COVID-19 victims [5]. However, COVID-19 remains a lethal disease that poses a significant threat to humanity. Many significant pharmaceutical and nonpharmaceutical companies have spent significant effort and money in the fight against this disease in recent years [6], as there was an immediate need to find a long-term therapeutic strategy, such as immunization [2]. Since the start of the coronavirus pandemic, experts have been working diligently to discover a way to stop the virus from spreading. The most pressing objective in the aftermath of such a public health crisis was the development of an effective vaccination [7], as vaccinating the global population is the most effective strategy to combat the COVID-19 pandemic. The promotion of these preventative methods, such as vaccination, is ethical and cost-effective and should be actively pursued by all physicians, particularly in the case of immune-compromised patients, e.g., patients with systemic sclerosis, who should be provided with the means to better protect their quality of life [8]. However, the public's apprehension regarding the available vaccines is a significant obstacle in the fight against the spread of COVID-19 [9].
Vaccines against COVID-19 protect the general public and limit viral spread [2]. The four key mechanisms investigated in this paper for the COVID-19 vaccines are inactivated virus, DNA, mRNA, and protein-based vaccines. DNA-based vaccinations transfer the DNA coding for the SARS-CoV-2 spike protein using viral vectors into cells; mRNA vaccines typically deliver mRNA into the cells via a lipid nanoparticle; protein vaccines are based on the spike proteins or their particles, and certain other vaccinations are based on inactivated viruses [10]. Vaccines are one of the most effective therapies for combating COVID-19, saving millions of lives each year. However, the ideal option is a vaccine that is efficacious, safe and does not cause serious adverse responses. Due to the lack of viable and licensed COVID-19 treatments, a vaccination development race has started, with 259 COVID-19 vaccine projects beginning on 11 November 2020. The fast development of vaccines has increased the possibility of vaccine-related safety concerns [11]. Many countries are developing vaccines in the aftermath of the COVID-19 pandemic to protect their populations [12]. Many vaccines have been made available earlier than planned due to their pressing need. New technology has also aided the development of far more effective vaccines; however, their potential adverse effects must be considered [6].

Side Effects (SEs) and COVID-19 Vaccination Resistance
The development of a COVID-19 vaccine was viewed as a critical strategy for ending the pandemic. Public acceptance, on the other hand, is based on people's ideas and perceptions of the vaccination [13]. The rates of vaccine hesitation and rejection are still higher, which may require legislative changes to make the vaccination program profitable [12]. One possible cause behind neglecting immunization could be the negative emotions such as anxiety, depression, anger, and irritability which have already been observed in many studies during quarantine periods. This occurs because psychosocial disturbances, such as relational loss and social rejection, cause changes in mind-body interplay [14]. Such hesitation has been linked to more negative beliefs that the vaccination would cause SEs or be unsafe [15]. The COVID-19 vaccine's adverse effects play a critical role in public trust in the vaccination and its administration technique [3]. An online self-administered questionnaire, completed in May 2020 among the Saudi population regarding vaccination views and the potential barriers preventing people from becoming vaccinated against COVID-19, cited SEs as major obstacles to vaccine uptake [13]. Similarly, in another study, seven attributes were evaluated to create vaccine choice sets: vaccine effectiveness, SEs, accessibility, number of doses, vaccination sites, length of vaccine protection, and a fraction of acquaintances vaccinated. Although all seven factors were found to have a substantial impact on respondents' vaccination decisions, and vaccination SEs were among the most relevant factors [16,17], the likelihood of a serious adverse SE was found to be a modest but significant cause of vaccination rejection. In comparison to rates of 1/1,000,000 general SEs, a significant adverse SE rate of 1/100,000 was more likely to discourage vaccine usage [18]. COVID-19 vaccinations have been expedited through the review process due to the lack of safety data. COVID-19 vaccines had a low level of public acceptance of 37.4%. Therefore public health officials must implement systematic interventions to reduce vaccine hesitancy and improve vaccine acceptance [19] and more studies are required to identify the benefits and SEs.

Selection and Collection of Data
The latest current available literature on COVID-19 immunization, COVID-19 vaccination updates, the studies on their reported SEs, updates on case reports presented with serious adverse SEs, their approval, authorization, and clinical phases were explored on Google scholar, Scopus, and Science Direct using the keywords "COVID-19 vaccination" or "COVID_19 immunization" or "SARS-CoV-2 vaccination" or "SARS-CoV-2 immunization" and "Side effects" or "Adverse effects" or "Safety studies", available up to November 2021.

COVID-19 Vaccinations' Approval/Authorization
Scientists across the world are working faster than ever to design and create vaccinations that can prevent the spread of COVID-19, with 21 vaccines already being distributed in countries around the world [20]. COVID-19 vaccines were previously available in three forms: messenger RNA-based vaccinations, adenoviral vector vaccines, and inactivated whole-virus vaccines. Some of them have passed phase 3 safety and efficacy trials and are now commonly utilized for COVID-19 infection prophylaxis [21], but now protein subunit forms of COVID-19 vaccines are also under consideration [22,23]. Thus far, the US Food and Drug Administration (FDA) has granted emergency use approval for three new COVID-19 vaccines: two messenger RNA-based vaccines (Pfizer and Moderna), and one adenoviral vector vaccine (Janssen) has received FDA approval [24]. In the event of a public health emergency, emergency use authorization (EUA) is provided for unlicensed medications and vaccines.  [20]. Eleven vaccines based on their authorization, approval, efficacy level, and utilization have been listed in Table 1.

Studies Reporting SEs of COVID-19 Immunizations
Previously, vaccination safety research only came from manufacturer-sponsored studies, but many other cross-sectional survey-based studies around the world have helped in the generation of vaccine-related safety data reports [3]. COVID-19 vaccine types and their SEs are illustrated in Figure 1.

Messenger RNA Based COVID-19 Immunization
The FDA granted Emergency Use Authorization (EUA) to two two-dose mRNA vaccines: BNT162b2 from Pfizer-BioNTech, for people aged ≥16 years; and mRNA-1273 Moderna for people aged ≥18 years [32]. Both vaccines employ either lipid nanoparticle delivery technology or a modified mRNA-delivery mechanism. Modified mRNA is used

Messenger RNA Based COVID-19 Immunization
The FDA granted Emergency Use Authorization (EUA) to two two-dose mRNA vaccines: BNT162b2 from Pfizer-BioNTech, for people aged ≥16 years; and mRNA-1273 Moderna for people aged ≥18 years [32]. Both vaccines employ either lipid nanoparticle delivery technology or a modified mRNA-delivery mechanism. Modified mRNA is used to encode the COVID-19 spike proteins, with mutant mRNA being added to lock them into the three-dimensional structure required to cause an interaction between the spike proteins and virus-neutralizing antibodies. They have a higher safety profile than other viral vaccines since they are not created with actual infections and are not incorporated into host DNA [28]. Both have been considered safe during pregnancy [29]. Messenger RNA vaccinations generate milder, less-frequent systemic adverse effects, but more localized SEs [9,33].

Pfizer-BioNTech (BNT162b2) COVID-19 Vaccination
Millions of people worldwide have been immunized with the Pfizer-BioNTech vaccination [24]. The Pfizer-BioNTech (BNT162b2) vaccine has shown good safety and efficacy in phase 3 trials and reduces the chances of SARS-CoV-2 infection after approximately 12 days of vaccination [34]. The Pfizer-BioNTech vaccine was associated with considerably greater rates of all forms of adverse reactions [35]. A selection of the minor SEs, which have been highlighted in ten studies on the Pfizer-BioNTech vaccine, is listed in Table 2. Among these eleven studies on Pfizer, eight studies reported headache; seven studies reported weakness/fatigue and myalgia/muscle/body pain; six studies reported local injection site/shoulder pain, chills/feeling cold, and fever; four studies reported enlarged lymph nodes and joint pain/arthralgia; three studies reported nausea/vomiting/GIT disturbances; one study reported cutaneous urticarial/morbilliform eruptions, weakness, hand numbness, mucosal lesions, taste disturbances, skin burning, rash, allergic reactions, dry cough, sore throat, brain fog, and decreased sleep quality. On the other hand, the prevalence of major or complex SEs has also been reported in these nine studies, including one study which reported adverse skin reactions, i.e., chilblains; zoster, herpes simplex, pityriasis rosea, etc.; two studies, which reported severe allergic responses such as anaphylaxis; one study which reported thromboembolic events such as a cerebrovascular accident, myocardial infarction, pulmonary embolism, acute hypertension (over 210/105mm Hg), and Bell's palsy. While exploring the data, available in the form of clinical case reports in Table 3, a total of twenty cases reported clinical complications which may have been linked with the Pfizer vaccination. Among these cases, eight belong to the onset of acute zoster ophthalmicus/varicella-zoster virus reactivation/shingles (herpes zoster); three belong to the lymphoproliferative disease and autoimmune adverse reactions (antineutrophil cytoplasmic autoantibody and severe immune thrombocytopenia); two cases pertain to acute immune thrombocytopenia; and one involves a clinical complication for takotsubo cardiomyopathy, multiple cranial neuropathies, and Guillain-Barré Syndrome. Some of the reported clinical cases for the COVID-19 vaccine and their SEs are illustrated in Figure 2.

Moderna (mRNA-1273) COVID-19 Vaccination
The Moderna vaccine, similar to the Pfizer vaccine, received FDA approval in its early clinical efficacy trials [29,63]. The SEs recorded for this vaccination are reasonably similar to those reported for other vaccines [63]. The minor SEs of Moderna has been highlighted in the five studies listed in Table 2. The most reported SEs include injection site pain, headache, fatigue, muscle pain, malaise, chills, joint pain, mucosal lesions, oral paresthesia, taste disturbance, pruritus, rash, itchy sensations in the mouth and throat, sensations of throat closure, muscles spasms, anorexia, decreased sleep quality diarrhea, flushing, nasal stiffness, and respiratory symptoms. Local injection site reactions, such as urticarial eruptions and morbilliform eruptions, have also been reported. While exploring the data available in the form of clinical case reports in Table 3, a total of fifteen cases have been reported thus far, which report complaints of clinical complications associated with the Moderna vaccination. Among these, there are two cases of severe hypersensitivity reactions with generalized pruritus, urticaria, tachycardia, chest, and neck urticarial, and mild facial angioedema; two complications of herpes zoster ophthalmicus (HZO) reactivation; one case of idiopathic thrombocytopenic purpura; four cases of COVID arm with erythematous plaques; three acute kidney complications with glomerulonephritis and proteinuria; two cases of encephalopathy; and one case of acute immune thrombocytopenia with generalized petechiae.

Viral Vector-Based COVID-19 Immunization
The non-replicating adenoviruses used in viral vector-based vaccines are safe for humans. This vaccine's technique has been in use for decades. Two distinct adenoviruses

Moderna (mRNA-1273) COVID-19 Vaccination
The Moderna vaccine, similar to the Pfizer vaccine, received FDA approval in its early clinical efficacy trials [29,63]. The SEs recorded for this vaccination are reasonably similar to those reported for other vaccines [63]. The minor SEs of Moderna has been highlighted in the five studies listed in Table 2. The most reported SEs include injection site pain, headache, fatigue, muscle pain, malaise, chills, joint pain, mucosal lesions, oral paresthesia, taste disturbance, pruritus, rash, itchy sensations in the mouth and throat, sensations of throat closure, muscles spasms, anorexia, decreased sleep quality diarrhea, flushing, nasal stiffness, and respiratory symptoms. Local injection site reactions, such as urticarial eruptions and morbilliform eruptions, have also been reported. While exploring the data available in the form of clinical case reports in Table 3, a total of fifteen cases have been reported thus far, which report complaints of clinical complications associated with the Moderna vaccination. Among these, there are two cases of severe hypersensitivity reactions with generalized pruritus, urticaria, tachycardia, chest, and neck urticarial, and mild facial angioedema; two complications of herpes zoster ophthalmicus (HZO) reactivation; one case of idiopathic thrombocytopenic purpura; four cases of COVID arm with erythematous plaques; three acute kidney complications with glomerulonephritis and proteinuria; two cases of encephalopathy; and one case of acute immune thrombocytopenia with generalized petechiae.

Viral Vector-Based COVID-19 Immunization
The non-replicating adenoviruses used in viral vector-based vaccines are safe for humans. This vaccine's technique has been in use for decades. Two distinct adenoviruses (AD16 and AD5) are employed, one in each dose of vaccine, with a 21-day interval [76].
The prevalence of systemic SE was higher in the AZD-1222 vaccine than in the Sputnik V and Covaxin vaccines [44].

AstraZeneca (ChAdOx1 nCoV-19) COVID-19 Vaccination
The AstraZeneca (ChAdOx1 nCoV-19) vaccine has shown good safety and efficacy in phase 3 trials and reduces the chances of SARS-CoV-2 infection after about 12 days of vaccination [34]. The AstraZeneca ChAdOx1 nCoV-19 (AZD1222) vaccine has been linked to thrombosis with thrombocytopenia syndrome (TTS) in 3/100,000 people, with high fatality rates reported in many countries. In Australia, the potential risks of the AZD1222 vaccine in younger adults who are unlikely to die from COVID-19 may outweigh the benefits [77]. A selection of the minor SEs that have been highlighted in five studies on the AstraZeneca vaccine is listed in Table 2. All five studies reported headache and myalgia/muscle/body pain; four studies reported weakness/fatigue, chills, nausea, diarrhea; three studies reported local injection site/shoulder pain and fever; two studies reported joint pain and tachycardia; and one study reported dry cough, shortness of breath, nasal discharge, swollen armpit, bruising, rash, allergic reactions, red felts on face, skin, oral mucosal lesions, and taste disturbances. The severe SEs reported in these studies were severe hypotension, generalized body aches, shortness of breath, and fever with a temperature greater than 39 • C. One study presented two clinical cases of transverse myelitis, a neurological disorder that might have been linked to the AstraZeneca vaccination.

Covishield (AZD1222)
Covishield is a COVID-19 vaccine developed in India. Covishield is currently in use and has nearly 90% effectiveness. It was developed by Oxford-AstraZeneca and is manufactured by the Serum Institute of India (SII) in Pune, Maharashtra. It employs the same technology that was used to develop vaccines for viruses such as Ebola, a chimp adenovirus, namely, ChAdOx1. This technology has been modified to carry the COVID-19 spike protein into human cells. A web-based survey study reported the SEs of the Covishield vaccine. The prominent SEs were mild fever (28.91%), myalgia (26.43%), cold and cough (8.16%), headache (6.74%), and local injection site pain (3.37%). Less-prevalent SEs included fatigue, diarrhea, rigors, joint pain, and nausea. Only 0.70% of recipients claimed severe symptoms with admission and observation in clinical setups [53].

Janssen (Ad26.COV2.S) COVID-19 Vaccination
The Janssen vaccine is based on the genetic modification of inactivated adenoviruses by the deletion of the E1 gene, which is replaced with the spike gene [78]. A VAERS-based study reported 64 anxiety-related events, as elaborated in Table 2. Other SEs included tachycardia, hyperventilation, dyspnea, chest pain, paresthesia, light-headedness, hypotension, headache, pallor or syncope, and fainting. Three clinical cases of severe immune thrombocytopenia (ITP), severe cutaneous adverse reaction, and Guillain-Barré syndrome (GBS) have been reported in its major complications, as shown in Table 3.

Sputnik V (Gam-COVID-Vac) COVID-19 Vaccination
Russia's first authorized vaccination was developed and manufactured wholly in the country, and its name alludes to the 1950s space race. To create the vaccine, the adenoviruses are mixed with the SARS-CoV-2 spike protein, which causes the body to respond with an immunological response [79]. Sputnik V was registered as Gam-COVID-Vac by the Russian Ministry of Health in August 2020, and it has been delivered in 61 countries globally since December 2020 [48]. A total of five studies have been added here; the SEs of Sputnik V are reported in Table 2. All five studies reported injection site pain; three studies reported fatigue, headache, swelling, and chills; four studies reported muscle or body pain and fever; two studies reported joint pain nodules or lymph nodes, diarrhea, and redness; and one study reported drowsiness, warmth, asthenia, malaise, insomnia, nausea, vomiting, and pruritus.

Covaxin Vaccine (BBV152)
India has produced a COVID-19 vaccine-namely, COVAXIN-that is an inactivated vaccine produced by Whole-Virion Inactivated Vero Cell-derived platform technology. It does not require reconstitution or sub-zero storage and comes in ready-to-use multi-dose vials that are stable between 2 and 8 • C. It cleared Phase I and II human clinical trials in July 2020. Vaccine-induced antibodies, according to the National Institute of Virology, can neutralize the UK variant strains as well as other heterologous strains. The effectiveness of the Covaxin vaccine is nearly 81% [53]. Local injection site pain, fatigue, muscular pain, and fever were described in a single investigation on the SEs of a Covaxin dose [44].

Sinovac
The most common local SE 54.6% was pain, while the most common systemic SEs were fatigue 39.2% and headache 34.1%. Two-thirds of individuals who were vaccinated reported at least one local or systemic SE, with women and people under the age of 35 being the most affected. Individuals who worked more than 8 h a day felt the vaccine's local adverse effects, such as increased hunger and weariness, more acutely [54]. A clinical case for severe acute asthma exacerbation was reported as a possible adverse effect of the Sinovac COVID-19 vaccination (Table 3).

Sinopharm (BBIBP-CorV/Vero Cells) COVID-19 Vaccination
The Sinopharm vaccine is a complete viral inactivated vaccine manufactured from Vero cells. These cells replicate the SARS-CoV-2 virus, which is subsequently treated with beta-propiolactone, which deactivates the virus by binding to its genes [28]. Sinopharm post-vaccination SEs remain modest and predictable for the first and second doses, with no cases of hospitalization, which help to reduce vaccine hesitancy [51,80]. Sinopharm vaccine recipients had a longer duration of adverse effects. The majority of these adverse effects are minor and curable [35]. A total of six studies have been documented here for SEs of Sinopharm in Table 2. All six studies reported headache; five studies reported fatigue; three studies reported injection site pain, body, or muscle pain; five studies reported headache; four studies reported fever; two studies reported myalgia, cough, flu, or nasal discharge, shortness of breath, abdominal pain, and diarrhea; one study reported lightheadedness, weariness, multiple bruises with productive bleeding; swelling in the legs and arms; chest pain, chills, arm pain, tenderness, lethargy, shivering, and rigors; malaise, myalgia, arthralgia, joint pain, sore throat, nausea, anxiety, and dizziness. Seven clinical cases of ocular adverse effects (episcleritis, anterior scleritis, acute macular neuroretinopathy, acute middle maculopathy, subretinal fluid); one case for anterior uveitis associated with juvenile idiopathic arthritis (JIA); and one case for bilateral anterior uveitis with reduced visual acuity in both eyes has been documented in the literature, as shown in Table 3.

COVID-19 Vaccinations' Reported Minor Side Effects
As elaborated in Table 1, the most-prevalent minor SE reported after COVID-19 vaccinations were localized reactions in the form of local injection site reactions, injection site/shoulder pain swelling, and soreness surrounding the area, whereas the mostprevalent generalized SEs were headache, fever, sweating, chills, tiredness, and fatigue. There were minor SEs in the nose, throat, and oral cavity, including throat infection or irritations, breath tightness, nasal stuffiness, flu-like symptoms, sensations of throat closure, oral mucosal lesions, paresthesia, and taste disturbance. The minor SEs of musculoskeletal symptoms included joint pain, muscular spasm, whole-body aches/myalgia, osteoarticular pain, back pain, and neck pain. The SEs of skin included skin rashes or allergic responses of urticarial eruptions, morbilliform eruptions, and pruritus. The minor SEs of the gastrointestinal system included nausea, vomiting, and diarrhea, while other SEs reported include fast heartbeat, dizziness, flushing, palpitations, brain fogging, mental confusion, anorexia, decreased sleep quality, drowsiness, hand numbness, enlarged lymph nodes, etc.

COVID-19 Vaccinations' Reported Major Side Effects
The adverse or major-severity SEs in Tables 1 and 2 reported from COVID-19 vaccinations on skin included zoster or herpes simplex flares such as varicella-zoster virus reactivation, chilblains, cosmetic filler reactions, and pityriasis rosea. The major SEs of the cardiovascular system (CVS) reported in studies include thromboembolic events such as thrombosis, cerebrovascular accidents, myocardial infarction, takotsubo cardiomyopathy, and pulmonary embolism. The major SEs of the central nervous system (CNS) included CNS demyelination, multiple sclerosis, syncope, transverse myelitis, encephalopathy, stroke, and acute disseminated encephalomyelitis. The major SEs of musculoskeletal system included Guillain-Barré syndrome, Bell's palsy and facial palsy. Ocular adverse effects included episcleritis, anterior scleritis, acute macular neuroretinopathy, acute middle maculopathy, subretinal fluid, and anterior uveitis associated with juvenile idiopathic arthritis (JIA). Severe immune system disturbances and autoimmune side effects were also observed, such as antineutrophil cytoplasmic autoantibody (ANCA)-associated vasculitis of acute kidney injury, severe immune thrombocytopenia, lympho-proliferative disease, hypersensitivity reaction, and severe cutaneous adverse reaction with panhypopituitarism secondary to craniopharyngioma resection. Furthermore, among adverse reactions, COVID arm with pruritic, erythematous plaques were reported. However, the link between the mildness and severity of SEs, along with the mechanism involved and other risk factor associations, is still under debate and requires proper investigative studies.

Conclusions
Twenty-seven studies on SEs and twenty-four case reports reporting fifty-six various clinical adverse effects of various COVID-19 vaccines have been overviewed in this study. Conclusive outcomes for local and systemic SEs revealed that the mRNA-based vaccines were more likely to be linked with localized adverse effects (e.g., injection site discomfort), while viral vector-based vaccines were found to be more common in imparting systemic SEs (e.g., headache/fatigue). Individuals who received Pfizer and AstraZeneca vaccines exhibited higher overall local site reactions when compared to those who received the Sinopharm vaccine. Regarding the SE severity, persistency, and duration, the AstraZeneca vaccine was found to have more persistent and severe SEs compared to other vaccines such as Pfizer; additionally, Pfizer's SEs were dominant in comparison to the Sinopharm vaccine. Overall, the vaccinations from Pfizer, AstraZeneca, and Sinopharm were judged to be safe, with Sinopharm having a lower number of adverse effects than the other vaccines. Pfizer was associated with greater rates, while Sinopharm was associated with longerduration SEs. On the other hand, the outcomes for age and gender revealed that females and youngsters, particularly individuals ≤ 43 years old, were found to be linked with a higher risk of adverse effects by both mRNA-based and viral vector-based immunizations. Sputnik V and Covaxin reported fewer SEs and better tolerance levels in the elderly. Injection site pain, fatigue, headache, muscle or body pains, and fever were the most reported SEs. Certain adverse effects, such as cutaneous reactions, herpes reactivation, ocular adverse effects, Bell's palsy, lymph nodes, anaphylaxis, thrombosis, myocardial infarction, cardiomyopathy, severe hypotension, multiple sclerosis relapse, syncope, stroke, GBS, facial palsy, myelitis, autoimmune SEs, acute disseminated encephalomyelitis, and multiple cranial neuropathies, were also reported in these studies. Overall, studies found that all immunizations were safe, with very few or no SEs; however, the form of SEs was shown to be more persistent in DNA-and mRNA-based vaccines, whereas inactivated viral vaccines were associated with longer-duration SEs. Overall, SEs were shown to be more prevalent in women and youngsters. Certain instances of adverse responses have also been observed, although their pathological relationship with COVID-19 immunization has yet to be determined.